title: Treatment of HIV-1-associated microsporidiosis and cryptosporidiosis with combination antiretroviral therapy.
abstract: BACKGROUND
  Enterocytozoon bieneusi and Cryptosporidium parvum cause chronic antimicrobial-resistant gastrointestinal infections in HIV-1-infected individuals. HIV-1 reverse transcriptase inhibitors delay the onset of opportunistic infections, but are not known to reverse established infections. HIV-1 protease inhibitors are more effective across a broader range of HIV-1-infected immune cells. Combination antiretroviral therapy that includes a protease inhibitor could improve immunity to E bieneusi and C parvum.
  
  
  METHODS
  HIV-1 infected patients with chronic microsporidiosis (five), cryptosporidiosis (three), or dual infection (one), were treated with combination therapy that included at least one HIV-1 protease inhibitor. Outcome measures were symptoms, weight, use of antidiarrhoeal and antimicrobial drugs, T-lymphocyte subsets, HIV-1 viraemia, stool microscopy, and biopsy by endoscopy.
  
  
  RESULTS
  All patients had complete clinical responses, gained a median 15 kg in weight, and ceased all antidiarrhoeal and antimicrobial therapies. Biliary cryptosporidiosis responded in both affected patients. Neither pathogen was detected in follow-up stool microscopy (eight of eight patients) or in biopsy samples by endoscopy (five of five). Intestinal architecture returned to normal in three patients. There was a dense CD8 lymphocyte and macrophage infiltrate and staining of intraepithelial E bieneusi with interferon-gamma before and after treatment, but little staining for CD4 or B lymphocytes, interleukin 10, or HIV-1 gp41. Five patients remained symptom-free after a median 13 months follow-up. Four patients had recurrent diarrhoea at 7-13 months (one with positive stool microscopy), associated with declining CD4 counts.
  
  
  CONCLUSIONS
  Combination antiretroviral therapy that includes a protease inhibitor can restore immunity to E bieneusi or C parvum in HIV-1 infected individuals, and result in complete clinical, microbiological, and histological responses. The persistent CD8 cell and macrophage infiltrate, and the rapid time to relapse in patients with declining CD4 lymphocyte counts, suggest that neither infection was eradicated.
authors.affiliation: HIV Medicine Unit and Centre for Immunology, St Vincent's Hospital, Sydney, Australia. acarr@stvincents.com.au
authors.forename: A
authors.initials: A
authors.lastname: Carr
authors.forename: D
authors.initials: D
authors.lastname: Marriott
authors.forename: A
authors.initials: A
authors.lastname: Field
authors.forename: E
authors.initials: E
authors.lastname: Vasak
authors.forename: D A
authors.initials: DA
authors.lastname: Cooper
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy* / Q000473:pathology; D000328:Adult; D000818:Animals; D018791:CD4 Lymphocyte Count / Q000187:drug effects; D003457:Cryptosporidiosis / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D016785:Cryptosporidium parvum / Q000302:isolation & purification; D003967:Diarrhea / Q000188:drug therapy; D004359:Drug Therapy, Combination; D005243:Feces / Q000382:microbiology; D005500:Follow-Up Studies; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D015497:HIV-1; D006801:Humans; D008297:Male; D016881:Microsporidiosis / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D008875:Middle Aged; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D016896:Treatment Outcome; D015430:Weight Gain
chemical_list: D017320:HIV Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors